A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin

Yasaman Malekizadeh (Lead / Corresponding author), Alison Holiday, Devon Redfearn, James A Ainge, Gayle Doherty, Jenni Harvey (Lead / Corresponding author)

    Research output: Contribution to journalArticle

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    Abstract

    A key pathology of Alzheimer’s disease (AD) is amyloid β (Aβ) accumulation which triggers synaptic impairments and neuronal death. Metabolic disruption is common in AD and recent evidence implicates impaired leptin function in AD. Thus the leptin system may be a novel therapeutic target in AD. Indeed, leptin has cognitive enhancing properties and it prevents the aberrant effects of Aβ on hippocampal synaptic function and neuronal viability. However as leptin is a large peptide, development of smaller leptin-mimetics may be the best therapeutic approach. Thus, we have examined the cognitive enhancing and neuroprotective properties of known bioactive leptin fragments. Here we show that the leptin (116-130) fragment, but not leptin (22-56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116-130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116-130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity. These findings establish further the importance of the leptin system as a therapeutic target in AD.
    Original languageEnglish
    Pages (from-to)4769-4782
    Number of pages14
    JournalCerebral Cortex
    Volume27
    Issue number10
    Early online date6 Sep 2016
    DOIs
    Publication statusPublished - 6 Sep 2016

    Fingerprint

    Leptin
    leptin (116-130)
    Alzheimer Disease
    Amyloid
    Neuronal Plasticity
    Aptitude
    AMPA Receptors
    Episodic Memory
    Synapses
    Cell Death
    Therapeutics
    Pathology
    Peptides

    Keywords

    • Alzheimer's disease
    • amyloid beta
    • AMPA receptor trafficking
    • episodic memory
    • hippocampus
    • synaptic plasticity

    Cite this

    Malekizadeh, Yasaman ; Holiday, Alison ; Redfearn, Devon ; Ainge, James A ; Doherty, Gayle ; Harvey, Jenni. / A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin. In: Cerebral Cortex. 2016 ; Vol. 27, No. 10. pp. 4769-4782.
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    abstract = "A key pathology of Alzheimer’s disease (AD) is amyloid β (Aβ) accumulation which triggers synaptic impairments and neuronal death. Metabolic disruption is common in AD and recent evidence implicates impaired leptin function in AD. Thus the leptin system may be a novel therapeutic target in AD. Indeed, leptin has cognitive enhancing properties and it prevents the aberrant effects of Aβ on hippocampal synaptic function and neuronal viability. However as leptin is a large peptide, development of smaller leptin-mimetics may be the best therapeutic approach. Thus, we have examined the cognitive enhancing and neuroprotective properties of known bioactive leptin fragments. Here we show that the leptin (116-130) fragment, but not leptin (22-56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116-130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116-130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity. These findings establish further the importance of the leptin system as a therapeutic target in AD.",
    keywords = "Alzheimer's disease, amyloid beta, AMPA receptor trafficking, episodic memory, hippocampus, synaptic plasticity",
    author = "Yasaman Malekizadeh and Alison Holiday and Devon Redfearn and Ainge, {James A} and Gayle Doherty and Jenni Harvey",
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    Malekizadeh, Y, Holiday, A, Redfearn, D, Ainge, JA, Doherty, G & Harvey, J 2016, 'A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin', Cerebral Cortex, vol. 27, no. 10, pp. 4769-4782. https://doi.org/10.1093/cercor/bhw272

    A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin. / Malekizadeh, Yasaman (Lead / Corresponding author); Holiday, Alison; Redfearn, Devon; Ainge, James A; Doherty, Gayle; Harvey, Jenni (Lead / Corresponding author).

    In: Cerebral Cortex, Vol. 27, No. 10, 06.09.2016, p. 4769-4782.

    Research output: Contribution to journalArticle

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    AU - Harvey, Jenni

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